An epigenetic marker panel for screening and prognostic prediction of ovarian cancer.
Aberrant CpG island hypermethylation is a common finding of cancers, which might be detectable in the tissue or serum of affected patients. We analyzed DNA methylation by methylation-specific polymerase chain reaction of 7 genes, which included secreted frizzled receptor proteins 1, 2, 4, 5 (SFRP1, 2, 4, 5), SRY-box 1 (SOX1), paired box gene 1 (PAX1) and LIM homeobox transcription factor 1, alpha (LMX1A) in primary tumor samples from 126 patients with ovarian cancer, 75 with a benign tumor and 14 with borderline malignancy of an ovarian tumor, and in the serum from 26 patients with ovarian cancer and 20 with a benign tumor. Six of 7 genes had higher methylation rates in patients with ovarian cancer than in borderline malignancy or benign tumor (p<0.001). The methylation of SFRP1, SFRP2, SOX1 and LMX1A genes correlated with recurrence and overall survival of ovarian cancer patients. Combining the data for SFRP1, SFRP2 and SOX1 genes gave a relative risk for recurrence of 3.19 (p=0.013) in patients with at least one gene methylation, and combining the data for SFRP1, SOX1 and LMX1A gave an RR for cancer-related death of 6.09 (p=0.010). Methylation analysis of tissues and serum revealed a significant correlation (kappa values, 0.332-0.598) and a highly sensitivity and specificity rates (73.08 and 75%) as a screening marker. In conclusion, promoter hypermethylation of specific genes in critical pathways is common in ovarian cancer and has potential as a prognostic factor and a promising serum marker for early screening.
Su
Her-Young
HY
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. su108868impo@gmail.com
Lai
Hung-Cheng
HC
Lin
Ya-Wen
YW
Chou
Yu-Ching
YC
Liu
Chin-Yu
CY
Yu
Mu-Hsien
MH
D001483:Base Sequence; D014408:Biomarkers, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D012306:Risk; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
D014408:Biomarkers, Tumor